Diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia (high blood sugar levels). Complications induced by diabetes, such as heart disease, stroke, hypertension, blindness, kidney failure, and amputation deprive the lives of 231,404 people in America as recently as 2007, making diabetes the seventh leading cause of death.
Glucose monitoring can reduce the occurrence rate and severity of complications caused by hyperglycemia or hypoglycemia. Thus, it is important to closely monitor abnormal blood sugar levels in diabetes patients so timely treatments (e.g., insulin injection, exercise, and diabetic diet, intake of carbohydrate) can be administered. This can be achieved by continuous glucose monitoring, which involves either noninvasive or minimally invasive detection of glucose. Noninvasive methods can extract interstitial fluid (ISF) glucose from the skin in minimally destructive approaches or measure blood glucose in contactless manners. Although noninvasive methods can be used for CGM, interferences, such as the complexity of skin structures, sweating, temperature, and exercise can impact the accuracy and reliability of the system, limiting their practical applications in CGM. Certain minimally invasive methods can use subcutaneous sensor implantation to monitor the glucose levels in ISF. In the steady state, ISF glucose concentration is identical to that in blood. However, when the blood glucose levels undergo rapid changes, time lags between the blood and the ISF glucose concentrations can occur.
Electrochemical glucose sensors, which use O2 and H2O2 as the mediators, can also be subject to errors induced by fluctuations of oxygen levels. In addition, redox-active species, such as ascorbic and uric acids, can compromise the selectivity and the accuracy of the glucose sensors. Other devices utilize artificial mediators (e.g., ferro/ferricyanide, hydroquinone, and ferrocene) as alternatives to oxygen for electron transfer. However, competition of oxygen with the artificial mediators and potential leaching and toxicity of these artificial mediators can hinder the in-vivo applications of these devices.
MEMS devices offer miniature sizes and rapid time responses, and are suited for implantable or noninvasive glucose sensors. MEMS technology can be used in developing electrochemical CGM sensors. MEMS affinity glucose sensors can use Con A, boronic-acid based monomers and polymers, and GBP as the glucose receptors and measure the glucose-induced changes in the properties of these receptors. For example, viscosity changes due to the binding of Con A or boronic acid-based polymers with glucose can be exploited by optical or electrical detection of microcantilever vibration, piezoelectric detection of flow resistance, and hall effect detection of microrotors.
There is a need to develop implantable glucose monitoring systems that offer improved long term accuracy and stability, low drift, resistance to environmental parameter fluctuations, easier calibration, as well as the capability of providing real-time report of a subject's glucose level via wireless telemetry.